Low back pain (LBP) is a major socio-economic concern in the US. While the exact cause of LBP is not clear, degeneration of the intervertebral discs (IVD) of the spine is believed to be the main origin. The IVD is the largest avascular structure in the human body, making transport of water and solutes in the discs an important mechanism of nutrition. Knowledge of transport and metabolic properties of important nutrients (e.g. glucose) is important in understanding pathophysiology involved in disc degeneration. Mechanical forces at the tissue level can affect physical signals at the cellular level and the way tissue remodeling changes physical signals through changes in tissue material properties and may also regulate cellular responses that may govern the initiation and progression of disc degeneration. Thus, determining changes in tissue properties as a result of mechanical strain is important in understanding the biological responses of IVD cells to force and other stimuli, and is therefore important in elucidating the etiologic factors involved in disc degeneration and LBP. The applicant's long-term goals are to (1) better understand the pathophysiology involved in the development of LBP;(2) further elucidate transport and metabolic properties in normal and degenerated IVD;and (3) develop new strategies for assessing and treating disc degeneration and LBP. The main objective of this proposal is to determine the effects of mechanical strain on glucose transport and metabolism in non-degenerated and degenerated human IVD tissues. In order to achieve this objective, the proposed plan is divided into three studies combining theoretical and experimental approaches. In Study #1, the strain-dependent glucose diffusivity in normal and degenerated human IVD tissues will be determined (Specific Aim #1) using a 1D unsteady state diffusion experiment and a custom designed diffusion cell. In Study #2, the strain-dependent partition coefficient of glucose in normal and degenerated human IVD tissues will be determined (Specific Aim #2) by measuring glucose concentrations within three baths equilibrated sequentially with tissue specimens under compressed and free-swelling conditions. In Study #3, the strain-dependent glucose consumption rate of porcine IVD cells will be determined (Specific Aim #3) by monitoring of glucose concentrations in bathing medium and using FEM analysis and theoretical curve-fitting with the Michaelis-Menten equation. Data obtained will be incorporated into a theoretical model to analyze transport and metabolic properties in IVD under mechanical strain. The outcome of these studies will provide insight into the etiological causes of disc degeneration and LBP and may also be used in the development of new strategies for treatment of LBP.